A New Model in Mice to Study the Wound Healing Response following Filtering Surgical Procedures for Glaucoma

Purpose. Failures of trabeculectomies are attributed to an exaggerated wound healing response at the episcleral level. We present a simple technique in mice that resembles trabeculectomies performed on larger mammals. We used it to study the role of growth factors in wound healing associated with loss of fistular patency. In addition, the effects of Decorin and Suramin were studied on the wound healing response. Methods. Using black C57B1/6 mice, we created a fistula from the subconjunctival space to the anterior chamber by external penetration with a 25 gauge needle through the bulbar conjunctiva. Eyes were examined by light microscopy at different times following surgery and evaluated for the presence of growth factors in the sclerosing wound by immunohistochemistry. In additional groups, Decorin and Suramin were applied topically. Results. The limbal/scleral wounds were primarily patent and closed rapidly. We found that within 1 day after surgery TGF β2 reached high intensity. TGF βl and PDGF A reached maximal intensity by day 2 and remained elevated for about a week. PDGF B was present at moderate intensity even before surgery. Myofibroblastic differentiation was observed from days 2 through 7. Suramin treated wounds showed a decrease of cells and delay in fibroblast maturation. TGF βl and TGF β2 levels persisted longer than in the controls, while PDGF A and PDGF B levels were decreased at all time points. Conclusions. The mouse model that we have developed mimics the process of wound healing and trabecular ablation. PDGF A as well as TGF βl and TGF β2 appear early in the process at high levels and are potential targets for interventive strategies to ensure channel patency. Decorin and Suramin have a distinct effect on the wound healing process and expression of growth factors therein.